Method in eye surgery

ABSTRACT

A method for prevention of migration of epithelial cells in a capsular bag of an eye of a mammal is provided. The method comprises removing the natural lens of the eye from the capsular bag; introducing an object with at least one sharp edge into the capsular bag, in such a way that said sharp edge contacts the inside of the capsular bag to form a barrier preventing migration of epithelial cells across said barrier; and injecting a lens-forming composition into the capsular bag.

RELATED APPLICATIONS

This application claims priority under 35 U.S.C. §120 as a continuationof U.S. application Ser. No. 10/438,685 filed May 15, 2003, which claimspriority under 35 U.S.C. §19 of Swedish Application No. 0201478-5 filedMay 16, 2002, and U.S. Application No. 60/381,262 filed May 17, 2002,and all of which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

The present invention relates to a method in connection with eyesurgery, especially in connection with replacement of the natural lensof the eye with an artificial lens. More particularly, the presentinvention relates to preventing migration of epithelial cells within thelens capsule of the eye in connection with such lens replacementsurgery.

BACKGROUND

The eye of a mammal is composed of a cornea, or clear outer tissue,which refracts light rays en route to the pupil, an iris which controlsthe size of the pupil, thus regulating the amount of light entering theeye, and a lens which focuses the incoming light through the vitreousfluid to the retina. The lens is embedded in a capsular bag. In theperfect eye, the light path from the cornea, through the lens andvitreous fluid to the retina is unobstructed. An obstruction or loss inclarity within these structures causes scattering or absorption of lightrays, resulting in diminished visual acuity. For example, the lens issusceptible to oxidative damage, trauma and infection.

As the body ages, the effects of oxidative damage accumulate, resultingin loss of lens flexibility and in denatured proteins that slowlycoagulate, reducing lens transparency. The natural flexibility of thelens is essential for focusing light onto the retina by the process ofaccommodation. Accommodation allows the eye to adjust the field ofvision for objects at different distances.

Lenticular cataract is a lens disorder resulting from the furtherprogression of protein coagulation and calcification. There are fourcommon types of cataracts: senile cataracts associated with aging andoxidative stress, traumatic cataracts which develop after a foreign bodyenters the lens capsule or following intense exposure to ionisingradiation or infrared rays, complicated cataracts which are secondary todiseases such as diabetes mellitus or eye disorders such as detachedretinas, glaucoma and retinitis pigmentosa, and toxic cataractsresulting from medical or chemical toxicity. Regardless of the cause,the disease results in impaired vision and may lead to blindness.

Treatment of such severe lens diseases requires surgical removal of thelens from the capsular bag. The surgical procedure typically involvesphacoemulsification, followed by irrigation and aspiration. Implantationof an intraocular lens (IOL) following the extraction of a cataract isnow a standard ophthalmic procedure. Current IOL:s include rigid,non-deformable lenses as well as rollable or foldable lenses.Furthermore, techniques wherein a low viscosity lens material isdirectly injected into the empty capsular bag and cured in situ as partof the surgical procedure to form an IOL, reducing surgical incisions toabout 1 mm, have been suggested. In such a process the capsular bag isused as a mould to form the shape of the lens and thereby contribute tocontrol its refraction.

In connection with the procedures described above for replacement of thenatural lens with an implant, there may arise complications. Some ofthese complications are characterized by a migration of epithelial cellswithin the capsule, which form a cell layer occluding the lens.

Prevention of cell migration has been addressed by differentinvestigators. Thus, it has been discovered that implantation of an IOLhaving sharp edges into rabbit eye lens capsules, such that the edges ofthe lens contact the inside of the capsular bag, leads to inhibition ofmigrating lens epithelial cells (Nish et al, Ophthalmic Surg Lenses29:5870594 (1998); Nishi and Nishi, J Cataract Refract Surg 25:521-526(1999); Nishi et at, J Cataract Surg 26:1543-1549 (2000)). The problemof epithelial cell migration is also addressed in U.S. Pat. No.6,319,282, in the context of using capsular equator rings formaintenance or establishment of an extended capsular diaphragm. U.S.Pat. No. 6,319,282 describes a capsular equator ring having sharp edgesfor the inhibition of migration of subcapsular epithelium cells. None ofthe above documents mention the problem of prevention of epithelial cellmigration in connection with injection of lens-forming materials intothe capsule. The injection of a lens-forming material into the capsule,which material subsequently forms, through curing thereof in situ orotherwise, an intraocular lens, poses additional problems as regards themigration of epithelial cells. This is so because of the fact that thelens formed will completely fill the lens capsule, and in particularwill not be removable in the manner of previously used flexible ornon-flexible IOL:s. Thus, the problems posed by epithelial cellmigration are more severe and difficult to address in the context ofinjected, lens-forming materials than in the situations described byprevious workers in the field.

SUMMARY OF THE INVENTION

It is therefore an object of the present invention to solve the aboveproblems through providing a method which offers a combination of therecently proposed techniques for injecting a material, which forms alens in situ after injection, with an approach to prevent epithelialcell growth during and after said injection.

Another object of the invention is to offer prevention of epithelialcell migration in connection with lens-forming material injection intothe lens capsule, which is amenable to use with any of a variety ofdifferent devices.

Still another object of the invention is to make possible the treatmentor prophylaxis of complications including secondary cataract formation,posterior capsule opacification, anterior capsule opacification,irregular growth and/or migration of epithelial cells etc. in thecontext of injection of a lens-forming material.

These objects, as well as others evident to the skilled person in lightof the present disclosure, are met by the invention as claimed. Thus, amethod for prevention of migration of epithelial cells in a capsular bagof an eye of a mammal is provided, which method comprises:

removing the natural lens of the eye from the capsular bag;

introducing an object with at least one sharp edge into the capsularbag, in such a way that said sharp edge contacts the inside of thecapsular bag to form a barrier preventing migration of epithelial cellsacross said barrier; and

injecting a lens-forming composition into the capsular bag.

The steps of the method of the invention need not be performed in anyparticular order. However, for practical reasons, the step of removingthe natural lens of the eye suitably precedes the steps of introducing asharp-edge object and injecting a lens-forming composition. The lattertwo steps may then be performed in any order.

The invention is thus based on the realization that the establishment ofa sharp edge against the capsular wall causes a sharp bend in thecapsular wall and a barrier which effectively hinders the spread andgrowth of epithelial cells, and, inventively, that this fact may beexploited in the context of injection of a lens-forming composition intothe eye.

BRIEF DESCRIPTION OF TIE DRAWING

The invention may be further understood in view of the drawing in which,

FIG. 1 provides a schematic view of an object introduced into thecapsular bag in accordance with one embodiment of the invention; and

FIG. 2 provides an enlarged cross-sectional view of the portion A setforth in FIG. 1.

DESCRIPTION OF PREFERRED EMBODIMENTS

The method of the invention is concerned with the prevention ofepithelial cell migration. Such migration may appear as a complicationfollowing eye surgery to remove the natural lens of the eye, and maygive rise to clouding of vision and other undesirable effects.Conditions characterized by migration of epithelial cells in the capsuleof the eye, which may be addressed prophylactically or therapeuticallyby the method of the present invention, include secondary cataracts,posterior capsule opacification (PCO), anterior capsule opacification(ACO) and irregular growth or migration of epithelial cells causingcapsular shrinkage.

The method of the present invention comprises removing the natural lensof the eye. This may be performed according to established practicewithin the art, for example by using a conventional surgical methodinvolving an ultrasound probe, such as a phacoemulsification methodinvolving aspiration. In order to facilitate the removal of the lensmatrix, introduction of an object and the refilling with lens-formingliquid material, a capsulotomy, e.g. a capsulorhexis, is suitablyprepared in the anterior wall of the capsular bag.

Further, the method of the present invention comprises introducing anobject with at least one sharp edge into the capsular bag, in such a waythat said sharp edge contacts the inside of the capsular bag. Thecontact of the sharp edge against the capsular bag forms a barrier tomigration of epithelial cells. It is preferred that this barrier isestablished along the equator of the inside of the capsular bag, so thatthe introduced object for example contacts at least 50% of the capsularbag wall along the equator. For optimal results, it is preferred that aslarge a part as possible of the capsular bag wall along the equator isprovided with the cell migration barrier. Thus, at least 75% is morepreferred, and at least 95% even more preferred. In the ideal case, theintroduced object establishes a sharp edge functioning as cell migrationbarrier along the whole of the capsular bag wall equator.

To fulfill this requirement, the introduced object may advantageously bean object suited for implantation into the capsule of the eye. Suitably,the object has roughly the shape of a filled or hollow cylinder, theradius of which is substantially larger than its height. The radius isfurthermore large enough that the object, when introduced into thecapsule, will “push against” the inside of the capsular wall, forexample along the equator. In this way, the sharp edge of the object isbrought to bear against the inside of the capsular bag, and the barrierto epithelial cell migration is formed.

For example, FIG. 1 shows a schematic view of an eye of a mammal whereinthe object 10 introduced into the capsular bag 20 is in the form of aring which pushes against the inside of the capsular bag along theequator. A portion A of the object 10 in the capsular bag is shown in anenlarged, cross-sectional view in FIG. 2 to illustrate an example of oneembodiment of the sharp edge 15 as it contacts the inside of thecapsular bag at area 25.

The object introduced into the capsule establishes a sharp edge againstthe capsular wall. The term “sharp edge” as used herein denotes an edgewith a radius that is preferably smaller than 2 micrometers (μm). Thesharp edge is needed for that pail of the device that is in contact withthe capsular tissue, and it must point to the direction from where themigrating cells come. The device with the sharp edge is also preferablypressed with enough pressure to that capsular tissue to prevent themigrating cells to “lift” the device and grow under it. The pressure maybe applied in different ways, such as by the internal pressure of theinjected lens-forming composition or by mechanical connection toanother, more or less opposite, part of the capsular bag. An example ofthis would be a sharp-edged ring on the posterior capsular side, whichis attached via rather stiff connectors to a ring on the anterior side.After filling with lens material, the capsular bag will be put undertension and thus exercise pressure on both rings. In this case, the ringmaterial must be such that it prevents cell migration over the side thatis not in touch with the capsular tissue. An extra sharp edge on this,interior, side of the ring, to prevent cell migration over this edge isalso preferred.

Among objects that are suitable for introduction into the capsular inthe context of the method of the present invention, mention is made ofcapsular equatorial rings, intraocular lenses and haptics forintraocular lenses, all of which should fulfill the requirement of beingprovided with at least one sharp edge along their outer circumference. Acapsular equatorial ring with sharp edges useful in the method of theinvention is described in U.S. Pat. No. 6,319,282, hereby incorporatedby reference. An intraocular lens with sharp edges useful in the methodof the invention may be any IOL of conventional materials or othermaterials, which present at least one sharp edge along the circumferenceof the lens. The acrylic IOL AcrySof® MA60BM, the standard PMMA IOL andthe silicon IOL CeeOn® Edge that were used in the experiments of Nishiand Nishi (J Cataract Refract Surg 25, 25:521-526 (1999); J CataractRefract Surg 26:1543-1549 (2000)) are examples of suitable intraocularlenses having the requisite sharp edges. As an alternative, the objectintroduced for the purpose of establishing a barrier against cellmigration may be a haptic of an intraocular lens, which haptic isprovided with at least one sharp edge. In this case, the IOL connectedto the haptic does not in itself need to be in close contact with thecapsular wall. Rather, the haptic or, in most cases of commerciallyavailable IOL:s, haptics play the role of pushing against the inside ofthe capsule. The primary function of the haptic or haptics of keepingthe IOL in place, is complemented by the added benefit of having a sharpedge that forms a barrier to cell migration.

Within the ambit of the method of the invention, the introduction of anobject as described above in the capsular bag serves the function ofproviding the sharp edge against the capsular bag wall, whereas theproblem of restoring the refractive power of the eye is solved by theinjection of a lens-forming material into the capsule. In the case wherethe object providing the sharp edge in itself has optical properties,such as when an IOL is used, these may be used in combination with theoptical properties of the injected lens-forming material. It is the aimof an injectible accommodating lens to restore accommodation, whichwould otherwise be lost after cataract surgery due to implanting of amonofocal IOL or simply due to aging of the eye (presbyopia). Normally,monofocal IOL patients and presbyopic humans need spectacles in order tohave good vision over all distances, from nearby (reading distance) toinfinity. The advantage of also having an artificial accommodating lens,made from an injected lens-forming composition, is ideally to enable thepatient to become independent of spectacles. That means that the baserefraction of the new lens must be such that, in combination with theaccommodating range of the new lens, the patient is able to see afocused image from near to infinity, without the help of spectacles. Thebase refraction is influenced by many factors, e.g. the length of theeye, the optical power of the cornea, the internal dimensions of the eyeand the refractive power of the refilled lens. This refractive power ofthe refilled lens may in turn be influenced by a number of factors, e.g.the shape of the capsular bag, the refractive index of the injectiblelens material, the degree of filling of the capsular bag. Throughimplanting of a sharp-edged lens inside the capsular bag in combinationwith the lens-forming injectible material, the refractive power can beinfluenced further. The procedure gives more degrees of freedom tocontrol the refractive power of the lens. Such a lens only as an effecton the refractive power when its refractive index differs from therefractive index of the lens-forming material.

As noted above, the method according to the present invention furthercomprises injecting into the capsular bag of a lens-forming composition.The composition consists of a partially polymerized material, which canundergo a curing process in the eye and thereby form a solid lensimplant. The lens implant acts as a substitute for the natural lens andaims to restore the features of the natural lens of a young eye.

Materials suitable for injection and subsequent formation of an IOL havebeen disclosed, for example in WO00/22459, WO00/22460 and WO0/76651.Briefly, a suitable lens-forming composition may be curable composition.The composition may further comprise polysiloxane. A preferredpolysiloxane composition for use in the method of the invention has aspecific gravity of greater than about 1.0, a refractive index suitablefor restoring the refractive power of the natural crystalline lens, anda viscosity suitable for injection of the composition through a standardcannula. These properties can be attained for example with a compositioncomprising a siloxane monomer —R_(a)R_(b)SiO—, wherein R_(a) and R_(b)are the same or different alkyl or phenyl groups, of which at least oneis substituted with at least one fluorine atom. A further usefulcomposition is one that comprises polysiloxane that is a terpolymer or ahigher polymer of three or more different siloxane monomer units. Aparticularly suitable lens-forming composition comprises polysiloxanethat is a terpolymer of (a) dimethylsiloxane, (b) methylphenylsiloxaneor diphenylsiloxane, and (c) trifluoroproyl-methylsiloxane monomers.Furthermore, the polysiloxanes forming part of such suitablelens-forming compositions may be provided with groups that are capableof being crosslinked, the composition then further comprising acrosslinking agent and, optionally, an effective amount of a catalyst.

Another type of material that has been proposed as suitable forinjection to form an IOL, and is therefore contemplated within thecontext of the present invention, is a hydrogel formulation.

As an exemplary embodiment of the method according to the presentinvention, the following steps are performed: First, the natural lens ofthe eye is removed by phacoemulsification involving preparing acapsulorhexis. Second, a capsular equatorial ring with sharp edges isinserted into the capsule through the capsulorhexis. Third, alens-forming composition comprising a mixture of functional andnon-functionalpoly(dimethyl-co-diphenyl-co-trifluoropropylmethyl)siloxanes is injectedthrough the ecapsulorhexis using a syringe.

The method according to the invention is applicable in any mammalincluding man. Most situations in which the method will be applicablewill probably concern attempts at restoring of eye-sight in a humanpatient.

1.-25. (canceled)
 26. Method for forming an intraocular lens in situ inan eye of a mammal, comprising: removing the natural lens of tile eyefrom the capsular bag; introducing an object with at least one sharpedge into the capsular bag, and positioning the object within thecapsular bag with the sharp edge contacting an inside wall of thecapsular bag to form a barrier preventing migration of epithelial cellsacross the barrier; injecting a lens-forming composition into tilecapsular bag to fill the capsular bag; and curing the lens-formingcomposition to form an intraocular lens in the capsular bag, wherein theformed lens completely fills the capsular bag and the sharp edge remainsin contact with an inside wall of the capsular bag after lens formationto prevent migration of epithelial cells across the barrier in thecapsular bag.
 27. Method according to claim 26, wherein the object withat least one sharp edge contacts the inside of the capsular bag along anequator of the capsular bag.
 28. Method according to claim 27, whereinthe object with at least one sharp edge contacts the inside wall of thecapsular bag along at least 50% of the equator of the capsular bag. 29.Method according to claim 28, wherein the object with at least one sharpedge contacts the inside wall of the capsular bag along at least 75% ofthe equator of the capsular bag.
 30. Method according to claim 29,wherein the object with at least one sharp edge contacts the inside wallof the capsular bag along at least 90% of the equator of the capsularbag.
 31. Method according to claim 26, wherein the object has a roughlycylindrical form, with a radius of the ccylindrical form beingsubstantially larger than a height of the cylindrical form.
 32. Methodaccording to claim 31, wherein the at least one sharp edge of the objecthas a radius of less than 2 μm.
 33. Method according to claim 31,wherein the object is a haptic of an intraocular lens, which haptic isprovided with at least one sharp edge.
 34. Method according to claim 31,wherein the object is an intraocular lens provided with at least onesharp edge.
 35. Method according to claim 34, wherein the object is afoldable intraocular lens.
 36. Method according to claim 34, wherein theobject is a non-foldable intraocular lens.
 37. Method according to claim26, wherein the lens-forming composition comprises polysiloxane andwherein the at least one sharp edge of the object has a radius of lessthan 2 μm.
 38. Method according to claim 26, wherein the lens-formingcomposition comprises polysiloxane.
 39. Method according to claim 38,wherein the lens-forming composition comprising polysiloxanec has aspecific gravity of greater thin about 1.0, a refractive index suitablefor restoring the refractive power of the natural crystalline lens, and[a viscosity suitable for injection of the composition through a standardcannula.
 40. Method according to claim 38, wherein the lens-formingcomposition comprises polysiloxane of a siloxane monomer unit—R₁R_(b)SiO—, wherein R_(a) and R_(b) are the same or different alkyl orphenyl groups, at least one of which is substituted with at least onefluorine atom.
 41. Method according to claim 38, wherein thelens-forming composition comprises polysiloxane that is a terpolymer orhigher polymer of three or more different siloxane monomer units. 42.Method according to claim 38, wherein the lens-forming compositioncomprises polysiloxane that is a terpolymer of (a) dimethylsiloxane, (b)methylphenylsiloxane or diphenylsiloxane, and (c)trifluoropropylmethylsiloxane monomers.
 43. Method according to claim38, wherein the lens-forming composition comprises polysiloxane havingcrosslinkable groups, and further comprises a crosslinking agent andoptionally an effective amount of a catalyst.
 44. Method according toclaim 26, wherein the lens-forming composition comprises a hydrogel. 45.Method according to claim 26, for prevention of posterior capsuleopacification.
 46. Method according to claim 26, for prevention ofanterior capsule opacification.
 47. Method according to claim 26, forprevention of a condition characterized by irregular growth or irregularmigration of epithelial cells in the capsular bag of the eye.
 48. Methodfor forming an intraocular lens in situ in an eye of a mammal,comprising: removing the natural lens of the eye from the capsular bag;introducing an object with at least one sharp edge having a radius ofless than 2 μm into the capsular bag and positioning the object withinthe capsular bag, with the sharp edge contacting an inside wall of thecapsular bag to form at barrier preventing migration of epithelial cellsacross the barrier; injecting a lens-forming, composition into thecapsular bag to fill the capsular bag; and curing the lens-formingcomposition to form an intraocular lens, wherein the formed lenscompletely fills the capsular bag and the object remains in the capsularbag with the sharp edge contacting an inside wall of the capsular bagafter lens formation by curing of the lens-forming composition toprevent migration of epithelial cells across the barrier in the capsularbag.